The invention relates to a novel method for preparation of 2-azetidinone-1-oxoacetate esters of formula (I) by oxidation of the corresponding N-(2-hydroxyacetate) esters of formula (II). The products obtained are valuable intermediates for preparation of antibacterial 2-substituted-2-penems.
Hamanaka, U.S. Pat. No. 4,619,924, which is hereby incorporated herein by reference, discloses antibacterial 2-alkylthiopenem derivatives of the formula ##STR4## wherein R.sub.1 is hydrogen or forms an ester group which is hydrolyzed in vivo and values for R.sub.2 include CH.sub.2 S(O.sub.m)CH.sub.3, CH.sub.2 CH.sub.2 S(O.sub.m)CH.sub.3 and ##STR5## where m and n are each 0, 1 or 2. In a preferred method the penems (IV) were obtained by the following reaction scheme. ##STR6## R.sub.3 is a silyl hydroxy protecting group, R.sub.4 =(C.sub.1 -C.sub.4)alkyl, PNB=p-nitrobenzyl.
Direct introduction of the desired SR.sub.2 group in the first step was not feasible because of side reactions which are known to take place in the conversion of acetidinone (VII) to the oxoacetate ester (VIII). This step is carried out, e.g., by condensation of (VII) with p-nitrobenzyloxalyl chloride in the presence of a tertiary alkylamine, each alkyl having from 1 to 4 carbon atoms, in the presence of reaction-inert solvent, e.g., dichloromethane, at 5.degree.-25.degree. C.
Use of compounds wherein R.sub.4 is other than alkyl, such as the above values for R.sub.2, above, and those for R.sup.2, below, especially the sulfoxides where m=1 gives rise to side reactions such as the Pummerer rearrangement as exemplified below. ##STR7##
For a review of the Pummerer reaction see, e.g., C. R. Johnson et al., J. Amer. Chem. Soc., 91, 682 (1969) and Durst, Advances in Organic Chemistry, 6, 356 (1969).